1. Field of the Invention
It has long been common practice for practitioners using a medical device to customize it on site. For example, practitioners may take a straight-ended catheter from stock and reshape it with the fingers, to achieve greater efficacy in a particular task. The present invention relates to a class of devices supplemented by computer supported designed-in variability, so that the user can make choices more accurately aimed at successfully accomplishing particular results.
The present invention relates to the field of delivery of materials into a patient, particularly at local sites within a patient using externally delivered devices to carry the materials to the desired site. The invention also relates to systems and processes for material delivery (especially pharmacologically active, view enhancing active or treatment active materials) to patients under Magnetic Resonance Imaging procedures.
2. Background of the Art
It is increasingly common and even necessary to administer a drug or other desired material to a carefully targeted part of the body. Currently such material is most often a solution or suspension of molecules, but in the future may include a suspension of nanoscopic devices. This targeted delivery is in contrast to conventional delivery methods where a drug is inserted into the bloodstream and treatment relies upon some of the drug finding the appropriate target. Targeted delivery has multiple advantages, when it can be done effectively. Much less of the drug is needed, which represents a double gain. Many drugs are costly, so the delivery of drugs in amounts greater than are needed for treating a specific area of a patient is wasteful and expensive. It is rare that any drug is wholly without negative effects (e.g., side effects, with reference to the desired result of the primary drug). In some instances, these adverse side effects arise only where the drug reaches a specific tissue. Therefore, restricting the drug to a target that does not include tissue that can be damaged avoids side effects completely. Even where that degree of precision in delivery is not possible, the side effects may be far more acceptable if limited to a small region around the target, with reduced impact on the body at large, while delivering the desired result on the target tissue at full strength. Even where the side effects are not directly life-threatening, it can be important to avoid them. For example, it is desirable to keep cancer chemotherapy drugs from the sites where they cause nausea and hair loss. That practice would be good both for patient morale and for patient persistence in taking the drug.
Some drug therapies use very strong or even toxic materials in the treatment, and even cryogenic treatments can cause collateral damage as the cryogenic material contacts non-targeted tissue. Hormonal treatments, where picogram delivery volumes are used because of the strength or activity of the material delivered and/or the limited area of treatment desired, can cause significant collateral damage when inappropriately delivered. This is particularly true in intraparenchymal procedures and other intracranial procedures where collateral damage, even on a small physical scale, can be very serious.
The majority of directed drug delivery systems tend to be essentially universal systems (intravenous or oral), indiscriminate local application (transdermal), or indiscriminate quasi-local (infusion from a catheter). Even the most advanced designs for MRI observable drug delivery as disclosed in U.S. Pat. Nos. 6,026,316; and 5,964,705 can only properly position the catheter, but do not provide specific structures that can adjust the rate and position of drug delivery from the catheter other than by standard fluid pressure control. Many different functions and controls are desirable in drug delivery systems, particularly with respect to the rate and direction of drug delivery. It would be a poor operational protocol to require essentially random direction positioning on a catheter of delivery outlets for a drug, cell culture, nanoscopic devices or other material, or require increased volumetric delivery, solely because the catheter could not be positioned with the outlets in an optimized position for desired delivery.
There are many different forms of drug delivery rate controls used in the medical field, both with intravenous, transdermal, and other forms of delivery. For example, U.S. Pat. No. 6,029,083 describes a xe2x80x9cfail-safexe2x80x9d iontophoretic drug delivery apparatus and a corresponding method is provided. The apparatus includes a current generating circuit for sending a current through a patch, error detection circuitry, and a control circuit. The control circuit controls the current generating circuit. When errors are detected in the apparatus, the control circuit stops the current and disables itself.
U.S. Pat. No. 6,017,318 describes a feedback controlled drug delivery system that includes the automated sampling and analysis of a patient sample and dosing the patient based on the analysis. Automated sampling may be performed by direct analysis of the patient sample, such as for the measurement of a blood sample coagulation state or a glucose level. The drug delivery system includes a sample set that has a bidirectional patient tube that allows for delivery of the patient sample to an analyzer, and at another time, the infusion of a therapeutic drug. A controller receives a measurement from the analyzer, and based on that measurement, adjusts the delivery of the therapeutic fluid. The sample set has a quick-clear Leur fitting that allows for more effectively clearing a first fluid from a Leur fitting when starting a second fluid. The system also has a reagent cassette holder that protects, using a foam gasket, a reagent on a sample slide. Further, the system provides an interlock apparatus that assures a sample tube is occluded by either or both a slide clamp and by a platen arm compressing the sample tube to a peristaltic pump.
U.S. Pat. No. 6,007,518 describes a fluid delivery apparatus comprising:
(a) a fluid delivery assembly having an outlet for delivering fluid from the apparatus, said fluid delivery assembly including:
(i) a base;
(ii) means defining a conformable ullage overlaying said base for forming in conjunction therewith a reservoir having an outlet in communication with said outlet of said fluid delivery assembly;
(iii) a cover assembly connected to said base, one of said cover assembly and said base having a receiving chamber interconnected with said reservoir; and
(iv) a stored energy means for exerting forces on said means defining a conformable ullage, said stored energy means comprising at least one distensible membrane superimposed over said means defining a conformable ullage, said membrane being distensible by forces imparted thereon by said means defining a conformable ullage in response to fluids introduced into said reservoir, said forces establishing internal stresses within said distensible membrane, said stresses tending to return said distensible membrane toward a less distended configuration, said distensible membrane being generally conformable to the shape of said means defining a conformable ullage as said membrane is being distended thereby and also being generally conformable to the shape of said means defining a conformable ullage as said distensible membrane tends to return to said less distended configuration; and
(b) a fill assembly interconnected with said fluid delivery assembly for filling said reservoir.
U.S. Pat. No. 5,997,527 describes a delivery device having a first chamber containing an osmotic agent, a membrane forming a wall of the first chamber through which fluid is imbibed by osmosis, a second chamber containing a beneficial agent to be delivered, and a moveable piston separating the two chambers. In fluid communication with the second chamber is an orifice which comprises a slit valve. In the presence of pressure, the beneficial agent pushes through the slit, opening up a channel for delivery of the beneficial agent and creating flow. Because the slit remains closed in the absence of flow (or when the pressure is below the pressure required to open the slit), back diffusion of external fluids is eliminated when the slit is closed, which prevents contamination of the beneficial agent in the second chamber by external fluids. In addition, forward diffusion of the beneficial agent out of the capsule is prevented when the slit is closed. The slit valve opens only to the minimum dimension required to allow the flow generated by the osmotic pumping rate. The slit valve also allows a flow path to open around any obstruction in the slit valve to prevent clogging.
U.S. Pat. No. 5,988,211 describes a method and apparatus for control of flow through an I.V. system, not a catheterized delivery system. That I.V. system comprises an I.V. Flow Controller incorporating an adjustable, differential pressure regulator that provides a constant but adjustable differential pressure across a fixed orifice. One end of the adjustment range provides shut-off and the other end full-flow. The adjustment range covers flow rates from zero to 250 ml/hr. At a given setting, the flow rate is independent of the total hydrostatic head height between the supply reservoir and a patient, provided the head height is greater than the pressure drop across the orifice at the maximum regulated flow rate, plus venous pressure, plus the pressure drop in the indwelling catheter.
U.S. Pat. No. 5,983,130 describes an electrically controlled delivery system comprising an electrotransport agent delivery device for delivering a therapeutic agent through a body surface, and a method for increasing agent delivery efficiency, is provided. The device includes a current controller which delivers a pulsating electrotransport current and peak current density Imax, Imax being greater than a critical current density level Ic above which the body exhibits a non-transitory higher agent delivery efficiency. Methods for increasing electrotransport delivery efficiency (E) of an agent through a body surface by creation of a higher agent delivery efficiency state are also provided.
U.S. Pat. No. 5,964,223 describes a method and apparatus for delivering a medicine to a patient via the patient""s respiratory system with control and efficiency. A nebulization catheter is positioned in the patient""s respiratory system so that a distal end of the nebulization catheter is in the respiratory system and a proximal end is outside the body. In a first aspect, the nebulization catheter may be used in conjunction with an endotracheal tube and preferably is removable from the endotracheal tube. The nebulization catheter conveys medicine in liquid form to the distal end at which location the medicine is nebulized by a pressurized gas or other nebulizing mechanism. The nebulized medicine is conveyed to the patient""s lungs by the patient""s respiration which may be assisted by a ventilator. By producing the aerosol of the liquid medicine at a location inside the patient""s respiratory system, the nebulizing catheter provides for increased efficiency and control of the dosage of medicine being delivered. In further aspects of the nebulizing catheter apparatus and method, alternative tip constructions, flow pulsation patterns, centering devices, sensing devices, and aspiration features afford greater efficiency and control of aerosolized medicine dosage delivery.
U.S. Pat. No. 5,961,483 describes novel methods and devices for iontophoretically administering therapeutic doses of cell adhesion receptor antagonists in a controlled manner through the skin. Such antagonist compounds include but are not limited to antagonists of the IIb/IIIa and xcex1vxcex23 integrins and related cell surface adhesive protein receptors. The present invention includes iontophoretic delivery devices comprising cell adhesion receptor antagonists. Such methods and devices are useful, alone or in combination with other therapeutic agents, for the treatment of thromboembolic disorders, angiogenic disorders, inflammation, bone degradation, cancer metastasis, diabetic retinopathy, restenosis, macular degeneration, and other conditions mediated by cell adhesion and/or cell migration and/or angiogenesis.
U.S. Pat. No. 5,941,868 describes Angiogenesis in cardiac and other tissues being promoted by the transmural delivery of angiogenic factors such as VEGF, FGF, EGF, and PDGF, through blood vessels and other body lumens into the surrounding tissue. Usually, the angiogenic factor is delivered using a catheter having infusion parts at its distal end. Optionally, the distal end of the catheter is radially expanded to engage the infusion parts directly against the blood vessel wall. A variety of catheter systems useful for the direct transmural infusion of angiogenic factors into the blood vessel wall are also well-described in the patent literature. Most commonly, balloon catheters having expandable distal ends capable of engaging the inner wall of a blood vessel and infusing an angiogenic factor directly therein are well-described in the patent literature. See, for example, U.S. Pat. Nos. 5,318,531; 5,304,121; 5,295,962; 5,286,254; 5,254,089; 5,213,576; 5,197,946; 5,087,244; 5,049,132; 5,021,044; 4,994,033; and 4,824,436. Catheters having spaced-apart or helical balloons for expansion within the lumen of a blood vessel and delivery of a therapeutic agent to the resulting isolated treatment site are described in U.S. Pat. Nos. 5,279,546; 5,226,888; 5,181,911; 4,824,436; and 4,636,195. A particular drug delivery catheter is commercially available under the trade name Dispatch(trademark) from SciMed Life Systems, Inc., Maple Grove, Minn. Non-balloon drug deliver catheters are described in U.S. Pat. Nos. 5,180,366; 5,112,305; and 5,021,044; and PCT Publication WO 92/11890. Ultrasonically assisted drug delivery catheters (phonophoresis devices) are described in U.S. Pat. Nos. 5,362,309; 5,318,014; and 5,315,998. Other iontophoresis and phonophoresis drug delivery catheters are described in U.S. Pat. Nos. 5,304,120; 5,282,785; and 5,267,985. Finally, sleeve catheters having drug delivery lumens intended for use in combination with conventional angioplasty balloon catheters are described in U.S. Pat. Nos. 5,364,356 and 5,336,178.
U.S. Pat. No. 5906,502 describes an apparatus for accurately infusing fluids into a patient at specific rates over an extended period of time and the method for making same. The apparatus includes one or more dispensers of a low profile, laminate or layered construction each having a stored energy source in the form of a distensible membrane or an elastomeric cellular mass, which in cooperation with the base, defined a fluid chamber having a fluid inlet and a fluid outlet. The apparatus further includes, in lieu of a rigid ullage, a high novel, conformable ullage made of yieldable materials. The conformable ullage uniquely conforms to the shape of elastomeric membrane as the membrane returns to its less distended configuration. This arrangement will satisfy even the most stringent delivery tolerance requirements and will elegantly overcome the limitations of materials selection encountered in devices embodying the rigid ullage construction. Additionally, with the novel ullage construction, the ullage can be located either between the base and the fluid to be delivered, or alternatively, can be located between the elastomeric membrane and the fluid to be delivered. Further, a plurality of sub-reservoirs can be associated with a single ullage thereby making it possible to incorporate a wide variety of delivery profiles within a single device.
U.S. Pat. Nos. 5,571,089; 5,542,926; and 5,522,800 describe a Low Profile Perfusion Catheter, for use in coronary angioplasty applications. Preferably, the catheter is provided with an inflatable dilatation balloon, and a perfusion lumen extending therethrough. The diameter of the perfusion lumen is enlargeable from a first, reduced diameter to a second, enlarged diameter. In one embodiment, an axially movable tubular support is movable within the lumen from a proximal, insertion position to a distal perfusion position. In another embodiment, the support is radially expandable. In a further embodiment, a porous drug delivery balloon is provided.
U.S. Pat. No. 5,385,547 describes a drug delivery device for coupling a first container including a beneficial agent to a second member. In an embodiment, the device includes a substantially hollow member having a cannula mounted within a wall that divides the substantially hollow member into a first and second section. The first section includes means for receiving at least a portion of a first container. The substantially hollow member includes a wall that defines an exterior of the first section that is substantially flexible. A number of different cannula and flow path structures within the hollow member are possible.
U.S. Pat. No. 5,498,236 describes a catheter suitable for introduction into a tubular tissue for dissolving blockages in such tissue. The catheter is particularly useful for removing thrombi within blood vessels. In accordance with the preferred embodiments, a combination of vibrating motion and injection of a lysing agent is utilized to break up blockages in vessels. The vessels may be veins, arteries, ducts, intestines, or any lumen within the body that may become blocked from the material that flows through it. As a particular example, dissolution of vascular thrombi is facilitated by advancing a catheter through the occluded vessel, the catheter causing a vibrating stirring action in and around the thrombus usually in combination with the dispensing of a thrombolytic agent such as urokinase into the thrombus. The catheter has an inflatable or expandable member near the distal tip which, when inflated or expanded, prevents the passage of dislodged thrombus around the catheter. The dislodged portions of thrombus are directed through a perfusion channel in the catheter, where they are removed by filtration means housed within the perfusion channel before the blood exits the tip of the catheter. Catheters that allow both low frequency (1-1000 Hz) vibratory motion and delivery of such agents to a blockage and a method for using such catheters are disclosed.
U.S. Pat. Nos. 5,800,392 and 5,569,198 describe an apparatus for delivering an agent to a treatment area. The apparatus includes a catheter that has a distal portion and a proximal portion. The catheter defines a lumen. A pressure regulator is in fluid communication with the lumen. A selectively inflatable member is also in fluid communication with the lumen, and is formed from a membrane. The membrane has first and second portions. The first portion defines pores sized from about 0.05 xcexc to about 1 xcexc and has a pore density from about 106 pores/cm2 to about 109 pores/cm2. The flux rate is from about 0.001 ml/(min-cm2-atm) to about 0.4 ml/(min-cm2-atm). The second portion is substantially impermeable.
U.S. Pat. No. 5,783,793 describes a laser drilling process capable of producing a plurality of holes in a pharmaceutical dosage form at high speed. The process utilizes a high power CO2 laser steered by an acousto-optic deflector together with various mirrors and optical components to achieve the correct beam path geometry, in order to produce an unlimited number of holes through the surface or coating of a dosage form, at rates up to 100,000 units or more per hour.
Even though restricted area targeting is highly desirable from a medical standpoint, this type of procedure adds to the traditional complexity of computing dosage and delivery rates. Instead of a single figure of blood concentration, controlled by the rates at which the drug enters and at which it diffuses, flows and is absorbed, metabolized or excreted by various tissues, concentration becomes a distinct time-varying number at each part of the body. Since the effects of a drug vary in complex ways on concentration (scopolamine, for example, is an anti-nausea drug in a narrow range of levels, neither too high nor too low), its administration must ensure that the concentration at the target tissue is correct for the desired effect. At the same time, the concentration at other points must minimize undesired effects (often, but not always, by minimizing concentration at such points). Planning treatments and procedures thus requires prediction and flexibility of drug (or material) delivery.
Prediction at real-time speed of drug transport is becoming possible due to improvements in computing machinery and in methodology (see the commonly assigned copending patent application of R. Raghavan et al., xe2x80x9cA Method and Apparatus for Targeting Material Delivery to Tissuexe2x80x9d, SLWK docket no. 723.032US1 and also the journal article by Paul Morrison et al., xe2x80x9cHigh-flow microinfusion: tissue penetration and pharmacodynamicsxe2x80x9d, American Journal of Physiology 266, p. R292-R305, 1994). This type of procedure permits planning not only of the timing and quantity of active material to be administered, but enables customized design of the form of the administering device for the best possible effect. The present invention provides designs for improved delivery systems that assist in improving the ability of the practitioner to implement the planned procedure.
Given scan data (magnetic resonance, CAT, etc.) on the anatomy and physiology of a patient, and in some cases on the transport of labeled materials in xe2x80x98scoutxe2x80x99 injections, one can construct a numerical model of transport which permits prediction of the evolving concentration level of the material to be administered.
Such prediction requires a model of the transport process in tissue, as described in the above identified copending patent application xe2x80x9cA Method and Apparatus for Targeting Material Delivery to Tissuexe2x80x9d. It also requires boundary conditions that specify the pressure or flow rate of fluid at sufficient distance from the injection device, and at the place(s) where the fluid leaves the device and enters the tissue.
The present invention defines a class of customizable injection devices or delivery instruments whose basic form is a stiff tube with holes of user-selectable size at several user-selectable places, whose use includes a method of selection and construction of a particular device from such a class of devices for a particular treatment procedure using computer-assisted means. Thus, the user may make selections among the available choices (such as selection of hole size, selection of hole location, etc.), and a method can be practiced for making such user-selection serve the goals of delivery of materials such as drugs, cells, or of devices sufficiently small and numerous to be delivered in fluid suspension. The tube is relatively stiff in the sense that it deflects by an amount between 0xc2x0 and 15xc2x0 under the stresses of insertion and placement at the end of a catheter, and varies less than 5 or less than 10% per cent in cross-sectional area when so deflected to the maximum of about 15 degrees.
The selection method may be practiced as follows. The user selects target tissues where the presence of the material is desired, and selects maximum and minimum target concentrations, and identifies tissues vulnerable to the material to be introduced, with maximum permitted concentrations identified in the region of the vulnerable tissues. This target information may be retained in the user""s consciousness, or input to the machine by use of an interface, such as a visual interface (e.g., with pre-procedure image information or real-time image information). The user may then specify a hole pattern (e.g., a number of holes, a distribution of holes, the size of holes, the position of holes, etc.), and see the predicted result with a selected time course of imposed pressure (or imposed flow rate) of the material at a specified concentration in injected fluid. Alternatively, e.g., if the desired concentration criteria have been communicated to a computer, the user may request the system to explore different patterns (as defined above) and injection plans to produce a result satisfying the input criteria, or coming as close to such satisfaction as is acceptable or possible.